Associations of cognitive intraindividual variability with Alzheimer's disease risk: A systematic review

Objective: Cognitive intraindividual variability (IIV) refers to an individual's variability in performance across cognitive measures and includes inconsistency and dispersion. While IIV has been studied in the context of cognitive aging, its application to Alzheimer's disease (AD) is more recent. This review synthesizes current research on IIV in AD risk, evaluating the role of IIV in distinguishing between cognitive stages and exploring associations with biomarkers to elucidate underlying mechanisms. Method: A systematic search strategy was employed across three electronic databases (PubMed, PsycINFO, and Web of Science) adhering to PRISMA guidelines. Forty-four studies met inclusion criteria and were included in the review. Results: Of the 44 reviewed articles, 19 examined inconsistency, 23 examined dispersion, and 2 studies examined both. Inconsistency-based studies broadly showed that greater IIV was associated with increased severity of cognitive impairment, particularly in mild cognitive impairment (MCI) and AD dementia. Findings of dispersion-based studies were mixed but largely revealed that higher IIV was associated with MCI and predicted incident dementia. Both IIV metrics suggested relationships between IIV and AD biomarkers (e.g. amyloidosis). Conclusions: Despite some variability in findings across studies, measures of inconsistency and dispersion are associated with cognitive impairment, cognitive decline, and AD biomarkers, even after adjusting for mean cognitive performance. The results expand upon prior studies, with more restrictive inclusion criteria, by including studies examining broad AD risk. There remains a lack of consensus on IIV assessment methods, complicating direct comparisons, but IIV measures have shown considerable potential for identifying individuals at risk of dementia.